This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteoarthritis &&#35;40;OA&&#35;41;is the most common rheumatic disease and the knee is the most often affected weight-bearing joint. While there are no cures for OA, obesity is a major risk factor. The modern concept of the role of obesity in chronic disease progression relates to a systemic low-grade pro-inflammatory state mediated by cytokines and adipokines produced by fat cells. An increase in omega-3 fatty acids in the diet decreases inflammation in rheumatoid arthritis. The use of omega-3 fatty acids consistently shows modest clinical improvements and a reduction in non-steroidal anti-inflammatory drugs in this population. We hypothesize that supplementing with the polyunsaturated fatty acids eicosapentaenoic acid &&#35;40;EPA&&#35;41;and gamma-linolenic acid &&#35;40;GLA&&#35;41;will significantly decrease the level of inflammatory cytokines in the blood when compared to a placebo. Even levels on the high end of normal values can negatively affect cartilage and bone metabolism. With their small size &&#35;40;less than 15kDa&&#35;41;, cytokines can readily diffuse from the systemic circulation into the joint space to act on joint tissues. Our primary outcomes will be measures of markers of inflammation, the inflammatory cytokines CRP, IL-6, TNF?, and the soluble receptor sTNFR1. Secondary measures will include mobility, self-reported physical function, and pain.